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beta cell

Xu Chen, Stefan Gustafsson, Thomas Whitington, Yan Borné, Erik Lorentzen, Jitong Sun, Peter Almgren, Jun Su, Robert Karlsson, Jie Song, Yi Lu, Yiqiang Zhan, Sara Hägg, Per Svensson, Karin E Smedby, Susan L Slager, Erik Ingelsson, Cecilia M Lindgren, Andrew P Morris, Olle Melander, Thomas Karlsson, Ulf de Faire, Kenneth Caidahl, Gunnar Engström, Lars Lind, Mikael C I Karlsson, Nancy L Pedersen, Johan Frostegård, Patrik K E Magnusson
Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWAS) in four European-ancestry cohorts, six SNPs in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta=0...
March 14, 2018: Human Molecular Genetics
Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Katarzyna Skrzypek, Yazmin Brito Barrera, Thomas Groth, Dimitrios Stamatialis
INTRODUCTION: Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability...
March 2018: International Journal of Artificial Organs
Anat Elmann, Alona Telerman, Rivka Ofir, Yoel Kashman, Orly Lazarov
Alzheimer's disease (AD) is the most prevalent cause of dementia in adults. Current available drugs for AD transiently alleviate some of the symptoms, but do not modify the disease mechanism or cure it. Therefore, new drugs are desperately needed. Key contributors to AD are amyloid beta (Aβ)- and reactive oxygen species (ROS)-induced cytotoxicities. Plant-derived substances have been shown to affect various potential targets in various diseases including AD. Therefore, phytochemicals which can protect neuronal cells against these insults might help in preventing and treating this disease...
March 15, 2018: Journal of Natural Medicines
Nicholette D Palmer, Hayrettin Okut, Fang-Chi Hsu, Maggie C Y Ng, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Jill M Norris, Carlos Lorenzo, Jerome I Rotter, Richard N Bergman, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease. Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study. Setting: Community-based. Participants: 1111 Mexican Americans...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Huizhen Fan, Chunyan Jiang, Baoyuan Zhong, Jianwen Sheng, Ting Chen, Qingqing Chen, Jingtao Li, Hongchuan Zhao
Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF- α ), transforming growth factor beta 1 (TGF- β 1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine's mechanism...
2018: Journal of Immunology Research
Onoufrios Tsavaris, Panagiota Economopoulou, Ioannis Kotsantis, Lazaros Reppas, Chrysanthi Avgerinou, Nikolaos Spathas, Maria Prevezanou, Amanda Psyrri
Chondrosarcoma is a rare malignancy characterized by the production of cartilage matrix, displaying heterogeneous histopathology and clinical behavior. Due to lack of effective treatment for advanced disease, the clinical management of metastatic chondrosarcoma is exceptionally challenging. Chondrosarcomas harbor molecular abnormalities, such as overexpression of platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, which are required for cancer development, progression, and metastasis. Pazopanib is a potent and selective multitargeted tyrosine kinase inhibitor, which co-inhibits stem cell growth factor receptor (c-KIT), fibroblast growth factor receptor (FGFR), PDGFR, and vascular endothelial growth factor receptor (VEGFR) and has demonstrated clinical activity in patients with advanced previously treated soft tissue sarcoma...
2018: Frontiers in Oncology
Jason T C Lee, Iryna Shanina, Yung Ning Chu, Marc S Horwitz, James D Johnson
Pancreatic beta-cells are selectively destroyed by the host immune system in type 1 diabetes. Thus, drugs that preserve beta-cell mass and/or function have the potential to prevent or slow the progression of this disease. We recently reported that the use-dependent sodium channel blocker, carbamazepine, protects beta-cells from inflammatory cytokines in vitro. Here, we tested the effects of carbamazepine treatment in female non-obese diabetic (NOD) mice by supplementing LabDiet 5053 with 0.5% w/w carbamazepine to achieve serum carbamazepine levels of 14...
March 15, 2018: Scientific Reports
Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Barnali Pramanik, Amy K O'Dowd, Donna M Williams, Clay B Frederick, Chan R Beals, S Aubrey Stoch, Helmut O Steinberg, David E Kelley
Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill-defined. To address this gap, we evaluated the effects of an intravenous (IV) infusion of native OXM on insulin secretory rates (ISR) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo-controlled, single dose crossover trials in 12 overweight and obese subjects without diabetes, and in 12 obese subjects with Type 2 diabetes (T2DM) respectively, using the GLP-1 analog, liraglutide as a comparator in the T2DM...
March 15, 2018: Diabetes
Dicson Sheeja Malar, Venkatesan Suryanarayanan, Mani Iyer Prasanth, Sanjeev Kumar Singh, Krishnaswamy Balamurugan, Kasi Pandima Devi
Amyloid beta (Aβ) formation is one of the neuropathological hallmarks of Alzheimer's disease (AD), which induces the generation of reactive oxygen species (ROS), further leading to the alteration of several signalling pathways. In the present study, vitexin has been evaluated for its neuroprotective activity against Aβ25-35 induced toxicity in Neuro-2a cells. Results of cell free studies indicated that vitexin significantly inhibited the aggregation of Aβ25-35 . Studies in Neuro-2a cells revealed that Aβ25-35 significantly affected the cell viability by inducing ROS mediated toxicity and apoptosis...
March 12, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Naoyuki Kitao, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Kiyohiko Takahashi, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
OBJECTIVE: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet. METHODS: Eight-week-old C57BL/6 J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient (Gck+/- ) and Irs2 knockout (Irs2-/- ) mice were exposed to either an SC or HF diet...
March 12, 2018: Metabolism: Clinical and Experimental
Quan-Bo Zhang, Yu-Feng Qing, Cong-Cong Yin, Li Zhou, Xian-Shuang Liu, Qing-Sheng Mi, Jing-Guo Zhou
BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of inflammatory and immune responses and are implicated in several immune disorders including gouty arthritis. The expression of miR-146a is upregulated in the peripheral blood mononuclear cells of patients with inter-critical gout when compared to normouricemic and hyperuricemic controls and those patients with acute gout flares. However, the role of miR-146a in the development of gout remains unknown. Here, we used miR-146a knockout (KO) mice to test miR-146a function in a monosodium urate (MSU)-induced gouty arthritis model...
March 15, 2018: Arthritis Research & Therapy
Thanh D Do, Joseph F Ellis, Elizabeth K Neumann, Troy J Comi, Emily G Tillmaand, Ashley E Lenhart, Stanislav S Rubakhin, Jonathan Sweedler
The mammalian dorsal root ganglia (DRG) are located on the dorsal roots of the spinal nerves and contain cell bodies of primary sensory neurons. DRG cells have been classified into subpopulations based on their size, morphology, intracellular markers, response to stimuli, and neuropeptides. To understand the connections between DRG chemical heterogeneity and cellular function, we performed optically guided, high-throughput single cell profiling using sequential matrix-assisted laser desorption/ionization mass spectrometry (MS) to detect lipids, peptides, and several proteins in individual DRG cells...
March 15, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Monica Raina, Amber M Bates, Carol L Fischer, Ann Progulske-Fox, Taher Abbasi, Shireen Vali, Kim A Brogden
BACKGROUND: Matrix metalloproteinases (MMPs) are zinc- or calcium-dependent proteinases involved in normal maintenance of extracellular matrix. When elevated, they contribute to the tissue destruction seen in periodontal disease. Recently, we found that human beta defensin 3 (HBD3), a cationic antimicrobial peptide, alters chemokine and proinflammatory cytokine responses in human myeloid dendritic cells exposed to Porphyromonas gingivalis hemagglutinin B (HagB). In this study, the hypotheses that HagB induces MMP production in dendritic cells and that HBD3 mixed with HagB prior to treatment alters HagB-induced MMP profiles were tested...
March 2018: Journal of Periodontology
Jonas Lorenz, Mike Barbeck, Charles James Kirkpatrick, Robert Sader, Henriette Lerner, Shahram Ghanaati
PURPOSE: In this prospective study, the regenerative potential and pathways of a new injectable bone substitute (IBS) material composed of beta-tricalcium phosphate (β-TCP) and hyaluronan were investigated for its application in alveolar bone regeneration within extraction sockets. MATERIALS AND METHODS: The bone substitute material was implanted in 44 extraction sockets after removal of teeth not worth preserving in the maxillary and mandibular arches of 21 patients...
March 15, 2018: International Journal of Oral & Maxillofacial Implants
Laurits J Holm, Martin Haupt-Jorgensen, Jesper Larsen, Jano D Giacobini, Mesut Bilgin, Karsten Buschard
Sphingolipids are a diverse group of lipids with important roles in beta-cell biology regulating insulin folding and controlling apoptosis. Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA. Here we tested the effect of L-serine supplementation on autoimmune diabetes development and blood glucose homeostasis in female NOD mice. We found that continuous supplementation of L-serine reduces diabetes incidence and insulitis score. In addition, L-serine treated mice had an improved glucose tolerance test, reduced HOMA-IR, and reduced blood glucose levels...
2018: PloS One
Aurore Quinault, Corinne Leloup, Geoffrey Denwood, Coralie Spiegelhalter, Marianne Rodriguez, Philippe Lefebvre, Nadia Messaddeq, Quan Zhang, Catherine Dacquet, Luc Pénicaud, Stephan C Collins
The rhythmic nature of insulin secretion over the 24h cycle in pancreatic islets has been mostly investigated using transcriptomics studies showing that modulation of insulin secretion over this cycle is achieved via distal stages of insulin secretion. We set out to measure β-cell exocytosis using in depth cell physiology techniques at several time points. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J islets in culture for 24h exhibit higher insulin secretion during the corresponding dark phase than in the light phase (Zeitgeber Time ZT20 and ZT8, respectively, in vivo)...
2018: PloS One
Charikleia Kelaidi, Antonis Kattamis, Filia Apostolakou, Christos Poziopoulos, Christina Lazaropoulou, Polyxeni Delaporta, Ino Kanavaki, Ioannis Papassotiriou
BACKGROUND: Levels of the angiogenic cytokines Placental Growth Factor (PlGF) and soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in Sickle Cell Disease and iron overload, but they have not been evaluated in Non-Transfusion-Dependent Thalassemia (NTDT). PATIENTS AND METHODS: We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation and tissue hypoxia...
March 15, 2018: European Journal of Haematology
Debanti Sengupta, Tae Jin Kim, Sepideh Almasi, Stuart Miller, Zsolt Marton, Vivek Nagarkar, Guillem Pratx
Radioluminescence microscopy is an emerging modality that can be used to image radionuclide probes with micron-scale resolution. This technique is particularly useful as a way to probe the metabolic behavior of single cells and to screen and characterize radiopharmaceuticals, but the quality of the images is critically dependent on the scintillator material used to image the cells. In this paper, we detail the development of a microscopy dish made of a thin-film scintillating material, Lu2O3:Eu, that could be used as the blueprint for a future consumable product...
March 15, 2018: Analyst
Francesca Mossa, Daniela Bebbere, Antonello Ledda, Giovanni P Burrai, Imane Chebli, Elisabetta Antuofermo, Sergio Ledda, Antonello Cannas, Francesco Fancello, Alberto S Atzori
Maternal nutrition during critical gestation periods impacts on offspring in later life; effects of high-starch maternal diet on testicular development in lambs were addressed. Dairy ewes were fed diets providing either 27% (Starch, S) or 11% (Fiber, F) of starch from mating to lambing (∼147 days; S147, F147) or for the last 75 days of gestation (S75, F75). Testes of single male lambs were measured and then sampled for histological and gene expression analyses at selected ages. Testicular dimensions and weight were similar among groups, but the total area of seminiferous tubules increased with age and tended to be higher (P = 0...
March 15, 2018: Molecular Reproduction and Development
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